DE4335370A1 - Process for the production of precious metal huminates - Google Patents

Description

The invention relates to a method for manufacturing stable connections between low molecular weight Humic substances and metals, mainly precious metals.

Find precious metal compounds and their preparations in various fields of medicine application.

Silver serves as a broad spectrum biocide Wound treatment agent for burns and as Scab formers.

Gold is used in the therapy of diseases of the rheumatic range.

Platinum is used in the application form cis-platinum in the treatment of malignant tumors.

The guaranteed effects of precious metal compounds are strong due to high toxicity Adverse effects that affect the therapeutic Narrow the width.

On the other hand, it is known from DE-A 41 29 872 that Humic acid-metal compounds physiologically good  are tolerated and also in the medical field be used.

It was expected that the medical Applicability of precious metal compounds improved is when the precious metals in the form of compounds with Humic acid, especially with low humic acid Molecular weight are present and used.

Unfortunately, it turned out that by usual Manufacturing processes such. B. by adding Metal salt solutions to aqueous humic acid solutions or partially neutralized alkali aluminate solutions with Precious metal salts are not produced stable huminates can be. The corresponding products or Complexes decompose and divorce after a short time the precious metals. This is in accordance with Other experts' observations.

So z. B. from Chem. Geol 102 (1-4), 53-71 (C. A. 118 (12): 106 459b) that gold (III) chloride is known by Humic substances under all conditions observed within 8 to 14 d to elementary, colloidal Gold is reduced.

It is therefore an object of the present invention To provide precious metal huminates that are so stable that they are also used in pharmaceutical preparations can be.

The task is solved by a method according to claims 1 and 2 and by corresponding Precious metal humate according to claims 3 and 4. Die Precious metal huminates according to the invention are suitable  especially as stabilizers for aqueous Alkali aluminate preparations, silver huminate as Broadband biocide, gold huminate for the therapy of rheumatic diseases and platinum humate Treatment of malignant tumors, according to the claims 5 to 8.

During the implementation of precious metal compounds with Humic acid or huminates not for stable integration the precious metal components leads to permanent success Introducing the precious metal component in certain Synthesis process of huminates at electrochemical and plasma chemical oxidation of alkaline, aqueous solutions more valuable phenolic compounds if a solution or a Hydrosol of a precious metal salt at the beginning of the Oxidation reaction of the solution of the polyvalent phenolic compound (s) in the anode or Reaction chamber is added.

Stable forms are formed in these synthetic processes Compounds of freshly synthesized humic acids with Precious metals, the precious metal humate. Up to one Precious metal content of 5 wt .-% are these huminates in aqueous solution at room temperature more than half Year stable. Even with a short-term stability test, a 24-hour temperature load of 90 ° C these solutions show no change.

Electrochemical and plasma chemical oxidation of polyvalent phenolic compounds for Production of low molecular weight alkali huminates is over EP-B 02 81 678, DE-A 41 34 379 and DE-A 41 34 384 known. The process variants and described there  Insert products can also be used to manufacture the Precious metal huminates according to the invention are used. However, the one disclosed in these writings is also Synthesis through multi-valued chemical oxidation phenolic compounds not for production stable precious metal humate.

Starting products for the process according to the invention can be all common polyhydric phenols, such as Pyrocatechol, resorcinol, hydroquinone, orcin, Gallic acid, protocatechic acid, pyrogallol, 2-oxyhydroquinone, phloroglucin or tetraoxybenzenes.

Likewise, as a polyvalent phenolic Compounds those of the general formula

are used, wherein R₁, R₃ and R₄ are the same or are different and an OH group or hydrogen represent R₂ is a CO or CH₂ group and R₅ and R₆ are the same or different and are hydrogen, represent an OH or methoxy group, where R₄, R₅ and R₆ are not all hydrogen at the same time.  

Examples of such connections are:
Narigenin
Eriodictyol
Hesperitin
Pelargonidine
Cyanidine
Delphinidin
Paonidine
Syringidine
Catechin, or epicatechin
Gallocatechin
Apigenin
Fisetin
Robinetin
Gossypetin
Luteolin
Fighter oil
Quercetin
Morin or myricetin
Preferred building blocks are quercetin and catechin.

The polyhydric phenols can be as pure substances or can be used in any mixture. They are in the form of 1-5% aqueous solutions submitted.

All precious metals can be used as precious metal components Salts in the form of aqueous solutions or hydrosols Precious metals gold, silver, mercury, rhenium as well the platinum metals ruthenium, rhodium, palladium, Osmium, iridium and platinum can be used.  

The hydrosols are commercial products that colloidal precious metal with a protective colloid (usually Gum arabic) included.

To implement the polyhydric phenols in one alkaline, aqueous solution dissolved. As lye can all alkali metal hydroxides, ammonia or strong amines be used in aqueous solution. Out economic reasons are sodium and Potassium hydroxide preferred.

For the production of huminates with a medium Molecular weight of 1000 D with a scattering range of The amount of alkali used is 300 to 1500 D according to the teaching of EP-B 02 81 678 in the range from 1.2 to 1.6 times the stoichiometric amount Phenolate formation of the polyhydric phenols, that is to say Neutralization of all phenolic OH groups necessary is. This results in a pH value of the reaction solution from 8 to 9 a.

The subsequent oxidation also occurs in Presence of precious metal compounds a automatic limitation of the reaction for products with an average molecular weight of 1000 D at one Spreading range from 300 to 1500 D.

To produce physiologically effective, not mutagenic humate with a molecular weight up to about 50 000 D, corresponding to DE-A 41 34 379 Set the amount of alkali so that the pH of the Reaction medium during the oxidation in the range of pH 8.5 to 11. The power supply is dosed so that the content of the polyhydric phenols  corresponding quinones is always less than 0.5%, based on the polyhydric phenols used, and that the oxidation reaction is stopped when the Quinone concentration drops despite power supply, or if the quinone concentration is below despite power supply 0.05%, based on the polyvalent used Phenols, has dropped.

The electrochemical oxidation takes place in one electrochemical reactor, the Oxidation rate by adjusting the Anode voltage and current density is determined.

The anode voltage can range from 1 to 20 V and the current density varies in the range from 0.5 to 4 A / cm² become.

The plasma chemical oxidation takes place in one known apparatus for corona discharge, the Oxidation rate by adjusting the Operating voltage and the field strength is determined. The Voltage can range from 20 to 250 kV Frequencies from 162/3 to 400 Hz and the field strength from Varies from 2 to 80, preferably from 10 to 20 kV / cm become. The pressure inside the discharge device is 0.05 to 3 kPa. Operation is both with Oxygen and air possible.

Both the electrochemical and the Plasma chemical oxidation is in the temperature range of 15 to 55 ° C, preferably carried out from 30 to 50 ° C. The temperature of the plasma is 150 to 300 ° C.  

Immediately after the start of the oxidation reaction when the Reaction mixture begins to turn brown, it becomes Reaction mixture in the electrochemical oxidation in the anode chamber during the plasma chemical reaction in the reaction tube an aqueous solution or a Hydrosol of a corresponding noble metal salt added in an amount that the concentration of the Precious metal in the newly formed reaction mixture in Range is 1 to 5 wt .-%.

After the oxidation reaction has ended, the pH value the reaction mixture to a value in the range of 4 set to 6 and buffered if necessary.

This is done either by adding acid or by Action of acidic ion exchanger and / or subsequent addition of an appropriate buffer solution (e.g. phosphate, tris or citric acid buffers).

Provided the neutralized and buffered solution contains unwanted suspended matter, it is now through a separation process such as centrifugation (10,000 to 30 000 xg) or filtering through a very fine-pored Filter material freed from these suspended matter. Although this solution for many applications directly can be used when using the Products as remedies by known Cleaning procedures like preparative Chromatography methods, ultrafiltration, Ultracentrifugation or electrodialysis cleaned and be freed from unwanted by-products.

A solution is obtained which is about 2 to 8% Contains precious metal humate. This solution can be done directly  be used or by carefully removing Water, for example by freeze drying to a 20% Be concentrated.

The solution obtained and the concentrated one is stable.

Examples Numbers in [] are CAS numbers example 1

100 g of an aqueous mixture of hydroquinone (3% w / w) are adjusted to pH 9 with KOH. The mixture will into the anode chamber of an electrochemical cell filled, the cathode chamber is with an aqueous KOH solution of pH 9 charged. The cell comes with a DC voltage of U = 2.5 volts operated, the pH value becomes constant by adding 1% KOH held. Identifiable at the start of the oxidation reaction by browning the reaction mixture, are in the Anode chamber 2 ml of an aqueous solution of Silver lactate (0.14 g [128-00-7] metered in. After The anodic oxidation ends for 12 hours continued, then the reaction mixture with neutralized with a suitable acidic ion exchanger and adjusted to pH 5. A clear, brown solution, even at temperatures of 90 ° C remains stable for 24 hours.

The silver content is 2.5%.  

Example 2

Analogous to example 1 with pyrogallol and silver lactate [128-00-7] as starting materials.

The silver content of the huminate is 2.3%.

Example 3

Analogous to Example 1 with 2 g / 100 ml of hydroquinone and 0.075 g / 2 ml tetrachlorogold (III) acid trihydrate [16961-25-4] as starting materials.

The gold content of the huminate is 1.8%.

Example 4

Analogous to Example 1 with 4 g / 100 ml pyrogallol and 0.13 g / 2 ml tetrachloro gold (III) acid trihydrate [16961-25-4] as starting materials.

The gold content of the huminate is 1.6%.

Example 5

Analogous to Example 1 with 5 g / 100 ml of hydroquinone and 0.18 g / 2 ml hexachloroplatinic (IV) acid hydrate [16941-12-1] as starting materials.

The platinum content of the huminate is 1.3%.  

Example 6

Analogous to Example 1 with 3.5 g / 100 ml pyrogallol and 0.13 g / 2 ml hexachloroplatinic (IV) acid hydrate [16941-12-1] as starting materials.

The platinum content of the huminate is 1.4%.

Example 7

In a low temperature plasma tube, with oxygen 0.1 hPa and 15 kV / cm operated, 100 ml of a aqueous mixture of hydroquinone (3% w / w) with KOH is adjusted to pH 9.5. The Mix passes through the discharge zone, becomes at the bottom Collect the end of the tube by adding 1% KOH solution adjusted to pH 9.5 and the Storage vessel fed again.

Once the oxidation reaction, recognizable by Browning of the reaction mixture, begins 2 ml of an aqueous solution of silver lactate (0.14 g) [128-00-7] added. After the end of the addition, the reaction continued for 5 hours, then the mixture with neutralized with a suitable acidic ion exchanger. The result is a clear brown solution that also with Temperature load of 90 ° C stable for 24 hours remains.

The silver content is 2.6%.  

Example 8

Analogous to Example 7 with 3.7 g / 100 ml pyrogallol and 0.16 g / 2 ml silver lactate [128-00-7] as starting materials.

The silver content of the huminate is 2.3%

Example 9

Analogous to Example 7 with 3.5 g / 100 ml of hydroquinone and 0.12 g / 2 ml tetrachlorogold (III) acid trihydrate [1691-25-4] as starting materials.

The gold content of the huminate is 1.6%.

Example 10

Analogous to Example 7 with 4.5 g / 100 ml pyrogallol and 0.12 g / 2 ml tetrachlorogold (III) acid trihydrate [1691-25-4] as starting materials.

The gold content of the huminate is 1.3%.

Example 11

Analogous to Example 7 with 5 g / 100 ml of hydroquinone and 0.15 g / 2 ml of hexachloroplatinic (IV) acid hydrate [16941-12-1] as starting materials.

The platinum content of the huminate is 1.1%.  

Example 12

Analogous to Example 7 with 2.2 g / 100 ml pyrogallol and 0.08 g / 2 ml hexachloroplatinic (IV) acid hydrate [16941-12-1] as starting materials.

The platinum content of the huminate is 1.3%.

Claims (8)

1. A process for the preparation of noble metal humates, characterized in that a polyvalent phenolic compound is oxidized electrochemically in an alkaline aqueous solution, a solution or a hydrosol of a corresponding noble metal salt being added in the anode chamber after the start of the oxidation reaction of the alkaline solution of the polyvalent phenolic compound the reaction mixture is adjusted to a pH in the range from 4 to 6 after the end of the oxidation reaction. 2. Process for the production of precious metal huminates, characterized in that a polyvalent phenolic compound in alkaline aqueous Solution is plasma-chemically oxidized, in which Reaction tube at the beginning of the oxidation reaction the solution of the polyvalent phenolic Compound a solution or a hydrosol of one corresponding noble metal salt added and that Reaction mixture after completion of the Oxidation reaction to a pH in the range is set from 4 to 6.   3. Precious metal humate of low molecular weight Humic acids with a precious metal content of 1 to 5% by weight. 4. Compounds of the elements gold, ruthenium, With rhodium, palladium, osmium, iridium and platinum Medium molecular weight humic acids from 900 to 30,000. 5. Use of the noble metal huminates as Stabilizers for aqueous Alkali huminate preparations. 6. Use of silver huminate as a broad spectrum biocide. 7. Use of gold huminate for the production of Active substances for the therapy of rheumatic Diseases. 8. Use of huminates of the platinum elements Manufacture of drugs for treatment malignant tumors.